Abstract
e14079 Background: Panitumumab, a fully human monoclonal antibody targeting epidermal growth factor receptor has emerged as an effective therapy for metastatic colorectal cancer (CRC). Its efficacy in the treatment of other cancers is also undergoing extensive investigation. Its association with skin toxicity has been reported by several individual studies, but the overall risk has not been defined. We performed a systemic review and meta-analysis of published clinical trials to quantify its overall risk of skin rash in cancer patients. Methods: Databases including PubMed, abstracts presented at the American Society of Clinical Oncology conferences and the European Society of Medical Oncology until December, 2009 were searched to identify relevant studies. Eligible studies included phase II and III clinical trials in which cancer patients were treated with panitumumab as a monotherapy or in combination with chemotherapy. Incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using a fixed-effects or random effects model based on the heterogeneity of included studies. Results: A total of 2,503 patients with mainly CRC from 11 trials were included for analysis. The overall incidence of all-grade skin rash was 80.3% (95% CI: 68.0%–88.7%), with 8.6% (95% CI: 3.8%–18.6%) being high-grade (grade 3 or above). The overall incidence of all-grade acne-like skin rash was 57.6% (95% CI: 37.0%–75.8%), with 6.2% (95% CI: 4.5%–8.5%) being high-grade. In comparison with panitumumab monotherapy, combination with chemotherapeutic agents significantly increased the risk of high-grade skin rash (RR 2.51, 95% CI: 1.75-3.60, p < 0.001), but not all-grade skin rash (RR 1.02, 95% CI 0.98-1.07, p = 0.35). From randomized controlled studies, panitumumab significantly increased the risk of developing all-grade skin rash (RR 5.51, 95% CI: 2.79-10.90, p < 0.001) and high-grade skin rash (RR 49.2, 95% CI: 18.4–131.5, p < 0.001) in comparison with controls. Conclusions: Panitumumab was associated with a substantial risk of high-grade skin rash, particularly when combined with chemotherapy. Further studies are strongly recommended for the prevention and treatment of high-grade skin rash. No significant financial relationships to disclose.
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